tbuckley/cabot-search huggingface dataset:
The Impact of Germline Alterations in Appendiceal Adenocarcinoma
Authors: Michael B. Foote, Henry Walch, Yelena Kemel, Efsevia Vakiani, Paul Johannet, Margaret Sheehan, Walid Chatila, Sebastian Chung, Garrett M. Nash, Anna Maio, Jinru Shia, Diana Mandelker, Michael Berger, Nikolaus Schultz, Luis A. Diaz, Andrea Cercek, Zsofia K. Stadler
Journal: Clinical Cancer Research (2023)

Over 10% of assessed patients with appendiceal adenocarcinoma (AC) have a pathogenic (P) or likely pathogenic (LP) germline variant, including genes implicated in heritable gastrointestinal cancer syndromes, such as Lynch Syndrome. We defined the clinical and molecular impact of heritable alterations in AC to evaluate the need for dedicated appendiceal screening and prevention strategies in patients with LP/P germline variants.We performed an integrated germline and somatic molecular analysis for patients with confirmed AC. Patients underwent paired tumor-normal sequencing for up to 90 hereditary cancer-risk genes and 505 genes for somatic mutation profiling. We defined the co-occurrence of LP/P germline variants and second-hit pathogenic somatic alterations. The associations between germline variants and patient clinicopathologic features were also evaluated.Twenty-five out of 237 patients (10.5%) carried pathogenic or likely pathogenic germline variants in cancer susceptibility genes. Clinicopathologic characteristics and AC-specific survival were similar in patients with or without germline variants. Most (92%, N=23/25) patients with germline variants demonstrated no second-hit somatic alterations, including loss of heterozygosity. Two patients with a germline APC I1307K low-penetrance founder variant exhibited secondary somatic pathogenic alterations in APC. However only one patient tumor exhibited APC-mediated WNT-signaling dysregulation; a plausible consequence of multiple somatic APC mutations with no germline variant contribution. Four patients had germline variants in PMS2 or MSH2 associated with Lynch Syndrome, yet their cancers were microsatellite-stable.Germline variants are likely incidental without a contributory driver role in AC. AC screening in patients with germline variants is not clearly merited.
A Designer Strategy to Develop Novel Bispecific Cancer Therapeutic Antibodies
Authors: Rakesh Kumar
Journal: Clinical Cancer Research (2023)

Therapeutic antibodies selectively targeting EPHA2 with or without co-targeting another RTK have been limited to date. By integrating state-of-art proteogenomic, ex-vivo models, and shRNA screening approaches, a new designing strategy has now discovered a bispecific therapeutic antibody co-targeting EPHA2 and EGFR - which effectively inhibits tumor cell growth in various preclinical cancer models. This new antibody provides new tools to impair the acquired resistance to EGFR-directed therapies or co-target EPHA2 and EGFR in human tumor.
Associated deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in Switzerland, 2010 to 2019
Authors: Michael Gasser, Alessandro Cassini, Danilo Lo Fo Wong, Marcello Gelormini, Saskia Andrea Nahrgang, Walter Zingg, Andreas Oskar Kronenberg
Journal: Eurosurveillance (2023)

BackgroundCassini et al. (2019) estimated that, in 2015, infections with 16 different antibiotic-resistant bacteria resulted in ca 170 disability-adjusted life-years (DALYs) per 100,000 population in the European Union and European Economic area (EU/EEA). The corresponding estimate for Switzerland was about half of this (87.8 DALYs per 100,000 population) but still higher than that of several EU/EEA countries (e.g. neighbouring Austria (77.2)).AimIn this study, the burden caused by the same infections due to antibiotic-resistant bacteria ('AMR burden') in Switzerland from 2010 to 2019 was estimated and the effect of the factors 'linguistic region' and 'hospital type' on this estimate was examined.MethodsNumber of infections, DALYs and deaths were estimated according to Cassini et al. (2019) whereas separate models were built for each linguistic region/hospital type combination.ResultsDALYs increased significantly from 3,995 (95% uncertainty interval (UI): 3;327-4,805) in 2010 to 6,805 (95% UI: 5,820-7,949) in 2019. Linguistic region and hospital type stratifications significantly affected the absolute values and the slope of the total AMR burden estimates. DALYs per population were higher in the Latin part of Switzerland (98 DALYs per 100,000 population; 95% UI: 83-115) compared with the German part (57 DALYs per 100,000 population; 95% UI: 49-66) and in university hospitals (165 DALYs per 100,000 hospitalisation days; 95% UI: 140-194) compared with non-university hospitals (62 DALYs per 100,000 hospitalisation days; 95% UI: 53-72).ConclusionsThe AMR burden estimate in Switzerland has increased significantly between 2010 and 2019. Considerable differences depending on the linguistic region and the hospital type were identified - a finding which affects the nationwide burden estimation.
RabbitTClust: enabling fast clustering analysis of millions of bacteria genomes with MinHash sketches
Authors: Xiaoming Xu, Zekun Yin, Lifeng Yan, Hao Zhang, Borui Xu, Yanjie Wei, Beifang Niu, Bertil Schmidt, Weiguo Liu
Journal: Genome biology (2023)

We present RabbitTClust, a fast and memory-efficient genome clustering tool based on sketch-based distance estimation. Our approach enables efficient processing of large-scale datasets by combining dimensionality reduction techniques with streaming and parallelization on modern multi-core platforms. 113,674 complete bacterial genome sequences from RefSeq, 455 GB in FASTA format, can be clustered within less than 6 min and 1,009,738 GenBank assembled bacterial genomes, 4.0 TB in FASTA format, within only 34 min on a 128-core workstation. Our results further identify 1269 redundant genomes, with identical nucleotide content, in the RefSeq bacterial genomes database.
Bimetallic Ions Functionalized Metal–Organic‐Framework Nanozyme for Tumor Microenvironment Regulating and Enhanced Photodynamic Therapy for Hypoxic Tumor
Authors: Meng‐Meng Pan, Puze Li, Yan‐Ping Yu, Ming Jiang, Xiangliang Yang, Pei Zhang, Jing Nie, Jun Hu, Xu Yu, Li Xu
Journal: Advanced Healthcare Materials (2023)

Photodynamic therapy (PDT), as a light irradiation inducing reactive oxygen species (ROS) generation for cancer treatment, offers facile and promising solutions with respect to spatiotemporal control of ROS generation, and minimizes the systemic toxicity and side effects for highly precise tumor therapy. However, the PDT efficiency is often severely compromised by the complex tumor microenvironment (TME), such as the hypoxic condition and overexpressed antioxidants. Here, for the first time, a bimetallic ion-modified metal-organic framework nanozyme (Zr4+ -MOF-Ru3+ /Pt4+ -Ce6@HA, ZMRPC@HA) is designed. ZMRPC@HA with catalase (CAT) and glutathione oxidase (GSHOx) mimetic activities, can efficiently regulate TME by generation of O2 and deplete the GSH synergistically for enhancing the long-term PDT efficacy toward the hypoxic tumor. The in vitro cell inhibition and in vivo on tumor xenograft evaluations demonstrate the PDT strategy by using ZMRPC@HA can successfully inhibit the differentiation and proliferation of tumor cells under a 660 nm laser irradiation in deep tissues. These findings open a new avenue for the design of multimetallic ions functionalized MOF-based nanozymes with multienzyme mimetic activities toward the antitumor and various other biological applications.
Introme accurately predicts the impact of coding and noncoding variants on gene splicing, with clinical applications
Authors: Patricia J. Sullivan, Velimir Gayevskiy, Ryan L. Davis, Marie Wong, Chelsea Mayoh, Amali Mallawaarachchi, Yvonne Hort, Mark J. McCabe, Sarah Beecroft, Matilda R. Jackson, Peer Arts, Andrew Dubowsky, Nigel Laing, Marcel E. Dinger, Hamish S. Scott, Emily Oates, Mark Pinese, Mark J. Cowley
Journal: Genome biology (2023)

Predicting the impact of coding and noncoding variants on splicing is challenging, particularly in non-canonical splice sites, leading to missed diagnoses in patients. Existing splice prediction tools are complementary but knowing which to use for each splicing context remains difficult. Here, we describe Introme, which uses machine learning to integrate predictions from several splice detection tools, additional splicing rules, and gene architecture features to comprehensively evaluate the likelihood of a variant impacting splicing. Through extensive benchmarking across 21,000 splice-altering variants, Introme outperformed all tools (auPRC: 0.98) for the detection of clinically significant splice variants. Introme is available at https://github.com/CCICB/introme .
<i>MGMT</i> Methylation Status in Grades 2 and 3 Gliomas Is Important, but Is It Prognostic?
Authors: Kelli B. Pointer, Na Tosha N. Gatson
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Antimicrobial resistance monitoring in the Danish swine production by phenotypic methods and metagenomics from 1999 to 2018
Authors: Ana Sofia R. Duarte, Ana Rita Marques, Vibe D. Andersen, Helle B. Korsgaard, Hanne Mordhorst, Frederik D. Møller, Thomas N. Petersen, Håkan Vigre, Tine Hald, Frank M. Aarestrup
Journal: Eurosurveillance (2023)

BackgroundIn Denmark, antimicrobial resistance (AMR) in pigs has been monitored since 1995 by phenotypic approaches using the same indicator bacteria. Emerging methodologies, such as metagenomics, may allow novel surveillance ways.AimThis study aimed to assess the relevance of indicator bacteria (Escherichia coli and Enterococcus faecalis) for AMR surveillance in pigs, and the utility of metagenomics.MethodsWe collated existing data on AMR and antimicrobial use (AMU) from the Danish surveillance programme and performed metagenomics sequencing on caecal samples that had been collected/stored through the programme during 1999-2004 and 2015-2018. We compared phenotypic and metagenomics results regarding AMR, and the correlation of both with AMU.ResultsVia the relative abundance of AMR genes, metagenomics allowed to rank these genes as well as the AMRs they contributed to, by their level of occurrence. Across the two study periods, resistance to aminoglycosides, macrolides, tetracycline, and beta-lactams appeared prominent, while resistance to fosfomycin and quinolones appeared low. In 2015-2018 sulfonamide resistance shifted from a low occurrence category to an intermediate one. Resistance to glycopeptides consistently decreased during the entire study period. Outcomes of both phenotypic and metagenomics approaches appeared to positively correlate with AMU. Metagenomics further allowed to identify multiple time-lagged correlations between AMU and AMR, the most evident being that increased macrolide use in sow/piglets or fatteners led to increased macrolide resistance with a lag of 3-6 months.ConclusionWe validated the long-term usefulness of indicator bacteria and showed that metagenomics is a promising approach for AMR surveillance.
Changes in cancer mortality after Medicaid expansion and the role of stage at diagnosis
Authors: Justin M Barnes, Kimberly J Johnson, Nosayaba Osazuwa-Peters, K Robin Yabroff, Fumiko Chino
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Medicaid expansion is associated with improved survival following cancer diagnosis. However, little research has assessed how changes in cancer stage may mediate improved cancer mortality or how expansion may have decreased population-level cancer mortality rates. Methods Nationwide state-level cancer data from 2001 to 2019 for individuals ages 20-64 years were obtained from the combined Surveillance, Epidemiology, and End Results National Program of Cancer Registries (incidence) and the National Center for Health Statistics (mortality) databases. We estimated changes in distant stage cancer incidence and cancer mortality rates from pre- to post-2014 in expansion vs nonexpansion states using generalized estimating equations with robust standard errors. Mediation analyses were used to assess whether distant stage cancer incidence mediated changes in cancer mortality. Results There were 17 370 state-level observations. For all cancers combined, there were Medicaid expansion–associated decreases in distant stage cancer incidence (adjusted odds ratio = 0.967, 95% confidence interval = 0.943 to 0.992; P = .01) and cancer mortality (adjusted odds ratio = 0.965, 95% confidence interval = 0.936 to 0.995; P = .022). This translates to 2591 averted distant stage cancer diagnoses and 1616 averted cancer deaths in the Medicaid expansion states. Distant stage cancer incidence mediated 58.4% of expansion-associated changes in cancer mortality overall (P = .008). By cancer site subgroups, there were expansion-associated decreases in breast, cervix, and liver cancer mortality. Conclusions Medicaid expansion was associated with decreased distant stage cancer incidence and cancer mortality. Approximately 60% of the expansion-associated changes in cancer mortality overall were mediated by distant stage diagnoses.
A deep learning framework for personalised dynamic diagnosis of graft fibrosis after liver transplantation: a retrospective, single Canadian centre, longitudinal study
Authors: Amirhossein Azhie, Divya Sharma, Priya Sheth, Fakhar Ali Qazi-Arisar, Rita Zaya, Maryam Naghibzadeh, Kai Duan, Sandra Fischer, Keyur Patel, Cynthia Tsien, Nazia Selzner, Leslie Lilly, Elmar Jaeckel, Wei Xu, Mamatha Bhat
Journal: The Lancet Digital Health (2023)
Evaluating the role of asymptomatic throat carriage of Streptococcus pyogenes in impetigo transmission in remote Aboriginal communities in Northern Territory, Australia: a retrospective genomic analysis
Authors: Jake A Lacey, Adrian J Marcato, Rebecca H Chisholm, Patricia T Campbell, Cameron Zachreson, David J Price, Taylah B James, Jacqueline M Morris, Claire L Gorrie, Malcolm I McDonald, Asha C Bowen, Philip M Giffard, Deborah C Holt, Bart J Currie, Jonathan R Carapetis, Ross M Andrews, Mark R Davies, Nicholas Geard, Jodie McVernon, Steven Y C Tong
Journal: The Lancet Microbe (2023)

Streptococcus pyogenes, or group A Streptococcus (GAS), infections contribute to a high burden of disease in Aboriginal Australians, causing skin infections and immune sequelae such as rheumatic heart disease. Controlling skin infections in these populations has proven difficult, with transmission dynamics being poorly understood. We aimed to identify the relative contributions of impetigo and asymptomatic throat carriage to GAS transmission.
Addressing the issue of a depleting health workforce in sub-Saharan Africa
Authors: Naomi Chinyere Chikezie, Deborah Oluwaseun Shomuyiwa, Ebere Angela Okoli, Ifebuche Maureen Onah, Oluwaseun Omolade Adekoya, Greatman Adiela Owhor, Adeniyi Ayinde Abdulwahab
Journal: The Lancet (2023)
The top 10 research priorities for the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris in the UK: results of a James Lind Alliance Priority Setting Partnership
Authors: Karen E Harman, Jag Barha, Jo R Chalmers, John K G Dart, Isobel Davies, Patricia  Ellis, Douglas Grindlay, Philip J Hampton, Sharleen Hill, Sharon Hockey, Antonia Lloyd-Lavery, Maggie McPhee, Ruth Murphy, Saaeha Rauz, Jane F Setterfield, Ingrid Thompson, Melanie Westmoreland, Christina Waistell
Journal: British Journal of Dermatology (2023)

To identify priorities for future research into the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris, we conducted a Priority Setting Partnership (PSP) using James Lind Alliance methodology. The top 10 priorities identified in this PSP represent the key questions that patients, carers and healthcare professionals have about the treatment of these diseases and which future research will hopefully address.
SPUMONI 2: improved classification using a pangenome index of minimizer digests
Authors: Omar Y. Ahmed, Massimiliano Rossi, Travis Gagie, Christina Boucher, Ben Langmead
Journal: Genome biology (2023)

Abstract Genomics analyses use large reference sequence collections, like pangenomes or taxonomic databases. SPUMONI 2 is an efficient tool for sequence classification of both short and long reads. It performs multi-class classification using a novel sampled document array. By incorporating minimizers, SPUMONI 2’s index is 65 times smaller than minimap2’s for a mock community pangenome. SPUMONI 2 achieves a speed improvement of 3-fold compared to SPUMONI and 15-fold compared to minimap2. We show SPUMONI 2 achieves an advantageous mix of accuracy and efficiency in practical scenarios such as adaptive sampling, contamination detection and multi-class metagenomics classification.
Protein arginine methyltransferase 5–mediated arginine methylation stabilizes Kruppel-like factor 4 to accelerate neointimal formation
Authors: He Liu, Xiaoliang Dong, Kunpeng Jia, Baohui Yuan, Zhengnan Ren, Xiaohua Pan, Jianjin Wu, Jiahong Li, Jingwen Zhou, Ru-Xing Wang, Lefeng Qu, Jia Sun, Li-Long Pan
Journal: Cardiovascular Research (2023)

Accumulating evidence supports the indispensable role of protein arginine methyltransferase 5 (PRMT5) in the pathological progression of several human cancers. As an important enzyme-regulating protein methylation, how PRMT5 participates in vascular remodelling remains unknown. The aim of this study was to investigate the role and underlying mechanism of PRMT5 in neointimal formation and to evaluate its potential as an effective therapeutic target for the condition.Aberrant PRMT5 overexpression was positively correlated with clinical carotid arterial stenosis. Vascular smooth muscle cell (SMC)-specific PRMT5 knockout inhibited intimal hyperplasia with an enhanced expression of contractile markers in mice. Conversely, PRMT5 overexpression inhibited SMC contractile markers and promoted intimal hyperplasia. Furthermore, we showed that PRMT5 promoted SMC phenotypic switching by stabilizing Kruppel-like factor 4 (KLF4). Mechanistically, PRMT5-mediated KLF4 methylation inhibited ubiquitin-dependent proteolysis of KLF4, leading to a disruption of myocardin (MYOCD)-serum response factor (SRF) interaction and MYOCD-SRF-mediated the transcription of SMC contractile markers.Our data demonstrated that PRMT5 critically mediated vascular remodelling by promoting KLF4-mediated SMC phenotypic conversion and consequently the progression of intimal hyperplasia. Therefore, PRMT5 may represent a potential therapeutic target for intimal hyperplasia-associated vascular diseases.
Diagnostic yield and safety of transbronchial lung cryobiopsy for diffuse parenchymal lung diseases diagnosis: Comparison between 1.7-mm and 1.9-mm probes
Authors: C. Ravaglia, F. Sultani, S. Piciucchi, A. Dubini, A.J. De Grauw, S. Martinello, S. Oldani, S. Maitan, F. Stella, V. Poletti
Journal: Pulmonology (2023)

Purpose of the research: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. Methods: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. Principal results: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. Conclusions: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.
Use of Large Language Models and Artificial Intelligence Tools in Works Submitted to <i>Journal of Clinical Oncology</i>
Authors: Kathy Miller, Emilie Gunn, Angela Cochran, Hal Burstein, Jonathan W. Friedberg, Stephanie Wheeler, Paul Frankel
Journal: Journal of Clinical Oncology (2023)

We don't want to change.Every change is a menace to stability.That's another reason why we're so chary of applying new inventions.-Aldous Huxley, Brave New WorldThe Journal of Clinical Oncology shares knowledge and expertise, fosters a robust interchange, and perpetuates valuable learning, all in service of improving outcomes of patients with cancer.To that end, JCO is more than just a collection of articles.The journal provides a forum for the exchange of ideas in which individual voices contribute their unique perspective and experience, providing the human context to the knowledge generated.That conversation between the author and the reader, albeit distant in time and space, is central to our purpose.Authors create text to provide the background and rationale for their work, describe the methods, delineate results, and share their interpretation.Figures display data visually, complementing and extending the results that were given in text form.Authors routinely use electronic tools to search the literature, correct grammar and spelling, analyze data, and format references.Recent advances in large language models (LLMs) and artificial intelligence (AI) such as ChatGPT have greatly expanded the electronic assistance available to authors.JCO's believes in the power of research to eliminate suffering from cancer.The potential for LLMs and AI to advance the pace of scientific development is both real and powerful; with great power comes even greater responsibility.A tool with such capabilities should be used thoughtfully and carefully.JCO recognizes that authors may find utility in using AI/LLMs in their scientific writing.However, LLMs/AI tools cannot and should not replace the human reasoning that is essential to our understanding of the world.Accordingly, we offer specific guidance on the appropriate use of these tools for manuscripts submitted to JCO.